REQUIREMENT OF 19K FORM OF SONIC HEDGEHOG FOR INDUCTION OF DISTINCT VENTRAL CELL-TYPES IN CNS EXPLANTS
REQUIREMENT OF 19K FORM OF SONIC HEDGEHOG FOR INDUCTION OF DISTINCT VENTRAL CELL-TYPES IN CNS EXPLANTS
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DOI：
10.1038/375322a0
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发表时间：
1995-05-25
期刊：
影响因子：
64.8
通讯作者：
MCMAHON, AP
中科院分区：
文献类型：
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作者：
MARTI, E;BUMCROT, DA;MCMAHON, AP
脊椎动物中枢神经系统中腹侧细胞类型的身份和模式取决于细胞相互作用（1）。例如，诱导一个专门的群体腹侧中线细胞，布尔板，似乎需要接触介导的信号由底层脊索，而扩散信号从脊索和底板可以诱导腹侧定位的运动神经元。Sonic hedgehog（Shh）是脊椎动物hedgehog家族成员，经加工产生两种肽（M（r）19 K和26/27 K），这两种肽由这两个组织中心分泌（2，30）。此外，在各种脊椎动物胚胎（3-5）和体外神经外植体（5）中的实验表明，Shh可以介导底板诱导。在这里，我们应用重组Shh肽神经外植体在无血清条件下。高浓度的Shh与基质结合诱导底板和运动神经元，并且向培养基中加入Shh导致运动神经元的剂量依赖性诱导。所有诱导活性都存在于高度保守的氨基末端肽（M（r）19 K）中。此外，特异性识别这种肽的抗体阻断脊索对运动神经元的诱导。我们建议，Shh作为一种形态素，诱导不同的腹侧细胞类型的脊椎动物中枢神经系统。
THE identity and patterning of ventral cell types in the vertebrate central nervous system depends on cell interactions(1). For example, induction of a specialized population of ventral midline cells, the Boor plate, appears to require contact-mediated signalling by the underlying notochord, whereas diffusible signals from the notochord and floor plate can induce ventrolaterally positioned motor neurons. Sonic hedgehog (Shh), a vertebrate hedgehog-family member, is processed to generate two peptides (M(r) 19K and 26/27K) which are secreted by both of these organizing centres(2,30). Moreover, experiments in a variety of vertebrate embryos(3-5), and in neural explants in vitro(5), indicate that Shh can mediate floor-plate induction. Here we have applied recombinant Shh peptides to neural explants in serum-free conditions. High concentrations of Shh bound to a matrix induce floor plate and motor neurons, and addition of Shh to the medium leads to dose-dependent induction of motor neurons. All inducing activity resides in a highly conserved amino-terminal peptide (M(r) 19K). Moreover, antibodies that specifically recognize this peptide block induction of motor neurons by the notochord. We propose that Shh acts as a morphogen to induce distinct ventral cell types in the vertebrate central nervous system.